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Genome-wide association analysis identified splicing single nucleotide polymorphism in CFLAR predictive of triptolide chemo-sensitivity

Overview of attention for article published in BMC Genomics, June 2015
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Title
Genome-wide association analysis identified splicing single nucleotide polymorphism in CFLAR predictive of triptolide chemo-sensitivity
Published in
BMC Genomics, June 2015
DOI 10.1186/s12864-015-1614-1
Pubmed ID
Authors

Lata Chauhan, Gregory D. Jenkins, Neha Bhise, Tanya Feldberg, Taraswi Mitra-Ghosh, Brooke L. Fridley, Jatinder K. Lamba

Abstract

Triptolide is a therapeutic diterpenoid derived from the Chinese herb Tripterygium wilfordii Hook f. Triptolide has been shown to induce apoptosis by activation of pro-apoptotic proteins, inhibiting NFkB and c-KIT pathways, suppressing the Jak2 transcription, activating MAPK8/JNK signaling and modulating the heat shock responses. In the present study, we used lymphoblast cell lines (LCLs) derived from 55 unrelated Caucasian subjects to identify genetic markers predictive of cellular sensitivity to triptolide using genome wide association study. Our results identified SNPs on chromosome 2 associated with triptolide IC50 (p < 0.0001). This region included biologically interesting genes as CFLAR, PPIl3, Caspase 8/10, NFkB and STAT6. Identification of a splicing-SNP rs10190751, which regulates CFLAR alternatively spliced isoforms predictive of the triptolide cytotoxicity suggests its role in triptolides action. Our results from functional studies in Panc-1 cell lines further demonstrate potential role of CFLAR in triptolide toxicity. Analysis of gene-expression with cytotoxicity identified JAK1 expression to be a significant predictor of triptolide sensitivity. Overall out results identified genetic factors associated with triptolide chemo-sensitivity thereby opening up opportunities to better understand its mechanism of action as well as utilize these biomarkers to predict therapeutic response in patients.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 27%
Other 2 18%
Student > Bachelor 1 9%
Student > Master 1 9%
Student > Ph. D. Student 1 9%
Other 0 0%
Unknown 3 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 27%
Agricultural and Biological Sciences 3 27%
Psychology 1 9%
Unknown 4 36%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 February 2016.
All research outputs
#5,501,936
of 7,289,383 outputs
Outputs from BMC Genomics
#4,274
of 5,404 outputs
Outputs of similar age
#154,912
of 224,453 outputs
Outputs of similar age from BMC Genomics
#212
of 244 outputs
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